This invention relates to a freeze drying apparatus having an improved automatic stoppering device and, more particularly, to a completely mechanical means for stoppering receptacles containing freeze dried materials in a closed chamber.
The well-known technique of freeze drying has provided an efficient means of preserving a wide variety of products for human and animal medicinal use. Freeze drying is similar to ordinary vacuum distillation except that the material to be dried must be solidly frozen before it is subjected to a high vacuum and controlled heat input. Under these conditions, the water content of the material is selectively removed by sublimation, going directly to the vapor state and bypassing the liquid phase. The residue is a dry powder devoid of water.
The basic components of most freeze drying systems include a vacuum chamber containing the material to be freeze dried, a condenser to trap sublimated water vapor, and a vacuum pump to provide a vacuum within the chamber. Additionally, a means of transferring heat of sublimation to the freeze drying material is required to drive the water vapor from the material to the condenser. The above components are normally assembled in combination and sold as units called freeze dryers or sublimators.
Frozen material to be dried may be placed in bulk in the vacuum chamber, but, in many applications a plurality of receptacles each containing small samples of frozen material are introduced into the chamber for drying. Use of receptacles permits the drying of large numbers of different samples at one time and eliminates the problem of contamination resulting from intermingling of samples.
It has been found that contamination may also occur if samples are exposed to the ambient air once the drying process is completed. Accordingly, a means to seal receptacles prior to their removal from the vacuum chamber into the ambient air was developed, which generally consists of a split stopper and a stoppering device. As is well known, split stoppers are formed with a slitted portion along the stem which is partially inserted into the neck of the receptacles, leaving a portion of the slit exposed through which vapors can escape during the drying process. Upon completion of the drying process, a stoppering device is used to force the split stoppers completely into the neck of the receptacles, closing off the slitted portion of the stopper and sealing the receptacles airtight.
One of the earlier stoppering devices, disclosed in U.S. Pat. No. 3,022,619 (strong et al.) consisted of a mechanical means of stoppering the receptacles upon completion of the sublimation process, which was bulky and complex in operation, making it prone to unexpected breakdowns. No built-in safety features were provided, and the stoppering process could not be reversed once initiated. Additionally, the device was not easily removable from the chamber so that bulk drying and stoppering of smaller samples could not take place within the chamber at the same time, as is often desirable.
An improved means of stoppering, disclosed in U.s. Pat. No. 3,795,986 (Sutherland et al.), was developed which simplified the mechanism of the above-named Strong et al. U.S. Pat. No. 3,022,619, but created certain disadvantages of its own. The Sutherland et al. patent discloses a bellows-type stoppering means, which employs a rubber bellows disposed between upper and lower plates. The plates are normally urged closed by spring means, but when the bellows are filled with compressed air, they expand, overcoming the force of the spring means to move the upper and lower plates apart. The expansion of the bellows continues until the lower plate contacts the stoppers of a group of receptacles disposed on a shelf positioned directly beneath the lower plate, which seals the receptacles airtight.
A problem associated with the bellows-type stoppering means, however, is the inherent limitations of the rubber material forming the bellows. The extreme pressure and temperature conditions within the vacuum chamber cause the rubber to crack and wear relatively quickly, requiring frequent replacement. In addition, rubber is a material having a certain degree of porosity. During the sublimation process, the vapors released from the materials undergoing drying may be absorbed by the bellows as they travel through the vacuum chamber to the condenser. These vapors may be released into the vacuum chamber by the bellows during subsequent drying operations, causing contamination of other samples.
Another form of mechanical stoppering device is described in U.S. Pat. No. 3,448,556 (Taggart) and illustrates a hydraulically-actuated platen which forces the bottom shelf upwardly to engage the shelf above it to stopper the bottles on the bottom shelf. The presence of a piston rod with oil and other contaminants on it in a vacuum chamber is obviously intolerable. Sealing the piston chamber from the vacuum chamber also presents a problem since one is under pressure and the other is under vacuum. To this inventor's knowledge, this unit never reached the commercial market, and the above deficiencies as well as others would hinder, if not prevent, commercial exploitation.
The rate of sublimation achieved by the devices disclosed in the Strong et al. patent and in the bellows-type stoppering device of Sutherland et al. is not uniform over the surface area of the shelf upon which the receptacles or bulk material is placed for drying. As mentioned above, the sublimation process requires that the freeze drying material be solidly frozen and then subjected to a high vacuum and controlled heat input. As discussed in detail below, in many freeze drying units, the heat of sublimation is provided by directing a heat transfer fluid through hollow shelves upon which the materials to be dried are placed. The refrigeration within the vacuum chamber is normally provided by cooling coils disposed about the outer surface of the chamber. The Sutherland et al. and Strong et al. patents mentioned above disclose apparatus which contact the chamber walls with a thermally conductive metal structure, upon which the shelves are mounted to support the material to be dried. The heat of sublimation introduced by the heat transfer fluid is not uniformly distributed over the surface area of the shelves since the contact of the stoppering apparatus with the chamber walls creates a transfer of thermal energy therebetween. The outer portions of the shelves are thus slightly cooler than the center, which prolongs the time required to dry samples placed at the outer edges of the shelves.